Synthesis and Antimicrobial Activity of 5-(R<Superscript>1</Superscript>-benzyl)-2-(R<Superscript>2</Superscript>-benzylidenehydrazono)-3-(2-furylmethyl)Thiazolidin-4-ones

3-Aryl-2-bromopropanoic acid esters react with furfurylthiosemicarbazones of benzaldehyde and 4-chlorobenzaldehyde to form 5-(R¹-benzyl)-2-(4-R-benzylidenehydrazono)-3-furfuryl-4-thiazolidinones (R = H, 4-Cl; R¹ = 4-Me, 4-F, 4-Cl). The antimicrobial activity of the synthesized compounds was studied, and it was established that only the compounds with R¹ = Me are active. The replacement of methyl group by halogen results in the loss of antimicrobial activity. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 5, pp. 20 – 22, May, 2005.     

Synthesis and Antimicrobial Activity of Complexes Based on 4-aryl-2-hydroxy-4-oxo-2-butenoic Acid <Emphasis Type="Italic">N</Emphasis>-heterylamides

Reaction of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-hetarylamides with copper, zinc, and cadmium dichlorides led to the formation of bis[3-aryl-1-(N-hetaryl)carboxamido-1,3-propanedionato]copper,-zinc, and-cadmium, respectively. Compounds with high antimicrobial activity were found among these products. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 7, pp. 14–16, July, 2008.     

Synthesis and Antiarrhythmic Activity of 5-Amino-<Emphasis Type="Italic">exo</Emphasis>-3-azatricyclo[5.2.1.0<Superscript>2,6</Superscript>]decan-4-one

Exo-2-amino-exo-3-aminomethylbicyclo[2.2.1]heptane (I) and 5-amino-exo-3-azatricyclo[5.2.1.0^2,6]decan-4-one (II) were synthesized and characterized with respect to antiarrhythmic activity. Compound II exhibited antiarrhythmic activity with ED₅₀ = 0.28 and 0.33 mg/kg on the aconitine and calcium chloride models of arrhythmia, respectively. Compound I did not show antiarrhythmic activity and exhibited acute toxicity corresponding to LD₅₀ = 450 mg/kg. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 9 – 11, June, 2005.     

Transplacental passage of Pt after treatment with the new triamine complex cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate,N<Superscript>4</Superscript>]-chloride platinum (II) monohydrochloride monohydrate

Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N⁴]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a monofunctional Pt triamine complex synthesized starting from cisplatin and procaine hydrochloride, characterized by a good antitumor activity coupled with low toxic effects and able to impair prenatal development of mice but at doses outside or just in the upper range of therapeutic doses. In the present paper the transplacental passage of DPR-derived Pt was investigated in CD1 mice on days 9, 13, 16 and 18 of pregnancy, 24 h after ip administration of 21 mg/kg DPR. For comparison, groups of mice were treated with an equivalent Pt-containing dose of cisplatin (10.7 mg/kg). Similarly to cisplatin, small amounts of Pt were detected in fetuses on day 9. From day 13 of gestation the concentration of DPR- and cisplatin-derived Pt increased up to the highest fetal concentrations detected on day 16. On day 18 the concentration of Pt decreased. Most importantly, on days 13–18 of pregnancy cisplatin-derived Pt was always significantly higher than that assayed after DPR administration. In addition, on day 13 of pregnancy Pt exposure of fetuses was significantly higher when dams were treated with cisplatin (AUC_0.5–24= 3.40 vs. 4.95 g·h/g). Finally, it is worth noting that serum decay of Pt after DPR or cisplatin administration in adult female mice was similar with AUC_0.13–2h s of 7.5 and 6.6 g·h/ml, respectively. When we determined the concentration of Pt into the main organs of fetuses from dams treated with either DPR or cisplatin on day 18 of gestation, we observed a different organ distribution. In fact, while the concentration of DPR-derived Pt was greater in the heart (1.08±0.30 vs. 0.78±0.35 g/g, p <0.10), an opposite situation was found in the kidney (0.51±0.20 vs. 0.69±0.22 g/g, p <0.05). In conclusion, our data show that DPR may pass through the placenta with an efficiency significantly lower than that of cisplatin. This finding may represent one of the possible causes of the lower embryotoxic/teratogenic effect of DPR as compared to cisplatin.     

New potential antihypoxants based on 2-ethyl-3-(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylcarbamoyloxy)-6-methylpyridine

It is established that succinic acid is capable of potentiating (synergism) the antihypoxic activity of 3-hydroxypyridine derivatives such as the succinate (Ia) and hydrochloride (Ib) of 3-(N,N-dimethylcarbamoyloxy)- 2-ethyl-6-methylpyridine. This effect makes it expedient to create new drugs containing a mixture of Ia or Ib and succinic acid derivatives that would possess antihypoxic, antiamnestic, and anticonvulsant activity. The antihypoxic activity of 3-hydroxypyridine drugs increases in the order emoxypin < mexidol < proxypin < Ia + succinic acid < Ib + succinic acid.     

Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>-PEI-RITC Magnetic Nanoparticles with Imaging and Gene Transfer Capability: Development of a Tool for Neural Cell Transplantation Therapies

Purpose  

To develop Fe₃O₄-PEI-RITC magnetic nanoparticles with multimodal MRI-fluorescence imaging and transfection capability, for use in neural cell replacement therapies.     

Synthesis and evaluation of antitumor activity of novel 2-[<Emphasis Type="Italic">N</Emphasis>-Methyl-<Emphasis Type="Italic">N</Emphasis>-(4-methyl-1,3-benzothiazol-2-yl)aminomethyl]-5,8-diacyloxy-1,4-naphthoquinones

A series of nine new compounds bridged by acyl groups at the 5,8-dihydroxyl group of DHNQ were synthesized and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor action in mice bearing S-180 cells in the peritoneal cavity was also assessed. Increasing the size of the acyl group (compounds 7–9) up to propyl increased the antitumor activity (T/C value), whereas the cytotoxicity of these compounds was comparable against L1210 (lymphocytic leukemia) and P388 (lymphoid neoplasm) cancer cells. Further increasing in the chain length (compounds 11–15) decreased the potency. Thus, acyl group chains of three carbon atoms is optimal for antitumor activity. The most potent compound of this series was 2-[N-methyl-N-(4-methyl-1,3-benzothiazol-2-yl)aminomethyl]-5,8-dipropylcarbonyloxy-1,4-naphthoquinone (compound 9) with a T/C (%) value of 354.     

Microwave-assisted synthesis,molecular docking and antimicrobial activity of novel 2-(3-aryl,1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)-8<Emphasis Type="Italic">H</Emphasis>-pyrano[2,3-f]chromen-4-ones

An efficient synthetic protocol of microwave-assisted synthesis of some novel 2-(3-aryl,1-phenyl-1H-pyrazol-4-yl)-8H-pyrano[2,3-f]chromen-4-ones 6a–j in excellent yields starting from 3-(3-aryl,1-phenyl-1H-pyrazol-4-yl)-1-(5-hydroxy-2H-chromen-6-yl)-propenones 5a–j was described. This approach offers the advantages of short reaction time (3–5 min), mild reaction conditions, high yields (80–88 %) and convenient operation. All the synthesized compounds were tested in vitro for their antimicrobial activity. The compounds 5h (Ar = 3-ethoxyphenyl), 6c (Ar = 4-chlorophenyl), 6e (Ar = 4-hydroxyphenyl) and 6i (Ar = 3,4-methoxyphenyl) were found to be potent against tested bacterial strains, and compounds 5g (Ar = 4-ethoxyphenyl), 6c (Ar = 4-chlorophenyl) and 6i (Ar = 3,4-methoxyphenyl) were found to be potent against tested fungal strains. The final compounds were subjected to molecular docking studies for the inhibition of enzyme DNA gyrase. The in silico molecular docking results are matching with the in vitro antimicrobial studies, and they may be considered as good inhibitor of DNA gyrase.     

Synthesis,biological evaluation of 2,3-disubstituted-imidazolyl/benzimidazolyl-quinazolin-4(3<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A series of disubstituted-quinazolin-4(3H)-ones derivatives have been synthesized and confirmed through IR, ¹H- and ¹³C-NMR, MS spectroscopy and elemental analysis. Synthesized compounds were screened for in vitro and in vivo anti-inflammatory using human red blood cell membrane stabilization method and carrageenan-induced rat paw edema. The antimicrobial potency was measured by disk diffusion method. The compounds with imidazole (3g) and benzimidazole nucleus (4b and 4f) displayed a significant anti-inflammatory activity by in vitro method. Moreover, the compounds 3d and 4a exhibited a significant anti-inflammatory activity in vivo. The compounds 3d, 3f and 4g were found to be active antimicrobial agents, when compared with reference drug ciprofloxacin and amphotericin B. Thus, these compounds can serve as promising leads for further biological studies.     

Synthesis and anti-inflammatory activity evaluation of novel 3-alkyl-6-(4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-4-yl)-3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">e</Emphasis>][1,3]oxazine derivatives

To discover new compounds with anti-inflammatory activity, a series of novel 3-alkyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine derivatives were synthesized and their structures were confirmed by spectroscopic techniques. In vivo anti-inflammatory activity of the synthesized compounds was determined using the xylene-induced mouse ear edema model. 3-Heptyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e] [1,3]oxazine and 3-p-tolyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine demonstrated higher anti-inflammatory activity (74.04?% and 64.99?%, respectively) at 0.5?h after intraperitoneal administration than the reference drug ibuprofen (62.65?%). Further, the time of peak effect after oral administration was 4?h for both compounds. Our results identify new compounds with anti-inflammatory activity in vivo that may have improved safety/side effect profiles relative to the currently approved nonsteroidal anti-inflammatory drugs.     

Synthesis and pharmacological investigation of novel 3-(benzyl)-2-substituted amino-3<Emphasis Type="Italic">H</Emphasis>-quinazolin-4-ones as analgesic and anti-inflammatory agents

A variety of novel 3-(benzyl)-2-substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-benzyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-benzyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from benzyl amine. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic index activities. The compound 3-benzyl-2-[N’-(1-ethyl-propylidene)-hydrazino]-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.